Admission Endothelial Activation and Stress Index and Echocardiographic RV-PA Coupling for Early Risk Stratification...

Background: Intermediate-risk acute pulmonary embolism (PE) is clinically heterogeneous, and early deterioration may occur despite initial normotension. The Endothelial Activation and Stress Index (EASIX) is a readily available laboratory index reflecting endothelial activation, cellular injury, renal-perfusion stress, and platelet-related thromboinflammatory burden. We investigated whether admission EASIX and echocardiographic right ventricular-pulmonary arterial (RV-PA) coupling assessed by the TAPSE/PASP ratio identify intermediate-risk PE patients at increased risk for an early adverse clinical outcome (EACO). Methods: This retrospective cohort study included 900 consecutive intermediate-risk acute PE patients admitted between 1 January 2020 and 10 June 2025. EASIX was calculated as LDH (U/L) × creatinine (mg/dL)/platelet count (10⁹/L). The primary endpoint was EACO within the first seven days after PE diagnosis during the index hospitalization, including hemodynamic decompensation, vasopressor/inotrope requirement, intensive care unit transfer, rescue reperfusion therapy, ventilatory support, cardiac arrest, or PE-related death. Hierarchical logistic regression, ROC analysis, calibration assessment, bootstrap internal validation, and 10-fold cross-validation were performed. Results: EACO occurred in 110 patients (12.2%). Patients with EACO had higher EASIX (2.28 [1.52-3.27] vs. 1.27 [0.86-2.00], p < 0.001) and lower TAPSE/PASP ratio (0.29 [0.23-0.36] vs. 0.42 [0.33-0.57], p < 0.001). log2-EASIX correlated inversely with TAPSE/PASP (Spearman rho = -0.30, p < 0.001). In the final combined model, log2-EASIX (OR 1.55 per doubling, 95% CI 1.14-2.10, p = 0.005) and TAPSE/PASP per 0.1-unit decrease (OR 1.36, 95% CI 1.10-1.68, p = 0.004) remained independently associated with EACO after adjustment for clinical variables, troponin, lactate, D-dimer, and C-reactive protein-to-albumin ratio. The final model showed higher discrimination than the clinical-laboratory model, although the absolute AUC increment was modest (AUC 0.920 vs. 0.904). Bootstrap optimism-corrected AUC was 0.910 and 10-fold cross-validated AUC was 0.904. Conclusions: Admission EASIX and impaired RV-PA coupling may provide complementary prognostic information for early risk stratification in intermediate-risk acute PE. Because this was a retrospective single-center study without external validation, these findings should be considered hypothesis-generating and should not be used as definitive treatment-escalation triggers before independent external validation.